Mutations in mitochondrial tRNA genes: Non-linkage with syndromes of wolfram and chronic progressive external ophthalmoplegiaa

Abstract

We have recently identified a point mutation in the mitochondrially encoded tRNALeu(UUR) gene which associates with a combination of type II diabetes mellitus and sensorineural hearing loss in a large pedigree. To extend this finding to other syndromes which exhibit a combination of diabetes mellitus and hearing loss we have sequenced all mitochondrial tRNA genes from two patients with the Wolfram syndrome, a rare congenital disease characterized by diabetes mellitus, deafness, diabetes insipidus and optic atrophy. In each patient, a single different mutation was identified. One Is an A to G transition mutation at np 12,308 in tRNALeu(CUN) gene in a region which Is highly conserved between species during evolution. This mutation has been described by Lauber et al. (1) as associating with chronic progressive external ophthalmoplegia (CPEO). The other is a C to T transition mutation at np 15,904 In tRNAThr gene. Both mutations are also present In the general population (frequency tRNALeu(CUN) mutation 0.16, tRNAThr mutation 0.015). These findings suggest that evolutionarily conserved regions in mitochondrial tRNA genes can exhibit a significant polymorphism in humans, and that the mutation at np 12,308 in the tRNALeu(CUN) gene is unlikely to be associated with CPEO and Wolfram syndrome. © 1992 IRL Press at Oxford University Press.